Technical Field
The present disclosure generally relates to biocompatible, dissolving microneedle structures with enhanced mechanical strength. More particularly, the present invention relates to microneedles containing well dispersed nanomaterials.
Background Information
Microneedles are tiny projections of micrometer dimensions and have the capability of delivering drugs, vaccines and other biomolecules to skin. This transdermal delivery platform has many advantages over conventional subcutaneous and intramuscular injection by needle and syringe. First, there is no or minimal pain, cross-infection and needle stick injuries. Second, microneedles can be designed to target a specific layer of skin. Third, there is potential for self-administration. Last but not least, it can be used when there is a significant first-pass effect of the liver that can prematurely metabolize drugs. Microneedle arrays are usually made of silicon, metals and polymers. Among them, polymer microneedle arrays are increasingly attractive because they are expected to be less expensive to mass produce than silicon or metal arrays and safer during application. Drugs and biomolecules can be incorporated into the interior of microneedles themselves when using dissolving polymers. During application, the polymer structure rapidly dissolves in skin, thereby releasing the drug and biomolecules, so there is no sharp waste.
Despite their promising features, dissolvable polymers generally have relatively weak mechanical properties. The need for combination of biocompatibility, robust mechanical properties and rapid dissolution rate severely limits the choice of polymer. Polyvinylpyrrolidone (PVP) and carboxymethylcellulose sodium salt (CMC) are commonly reported for use in dissolving polymer microneedles. For example, PVP microneedles were fabricated by either in-situ polymerization of monomers under UV conditions (using a 100 W UV lamp) or heating at 80° C. for 24 hours. These harsh conditions may seriously limit the incorporation of drug and biomolecules that are temperature or UV sensitive. On the other hand, CMC microneedles can be fabricated at room temperature, but CMC has weak mechanical properties. For example, the elastic modulus of CMC is only around 1 GPa. It is expected that the bioresorbable polymer microneedle size needs to be relatively large to reliably pierce human skin. This would apparently limit the density of microneedles on an array. However, recent study shows that small (base diameter or width <40 μm) and densely packed microneedles (over 10,000 microneedles per cm2) may lead to significantly enhanced vaccine efficacy when compared to large and sparsely packed ones. In addition, small microneedles can be easily dried during fabrication and dissolve rapidly in skin during application. Therefore, improving the mechanical properties of dissolving polymer microneedles could be beneficial in terms of drug efficacy and design flexibility as well as ease in fabrication and rapid dissolution in the skin.
Thus, a need exists for improved mechanical characteristics of dissolving microneedle arrays for transdermal delivery.